1. Field of Invention
The present invention relates generally to medical devices and methods for inhibiting restenosis in a blood vessel after an initial treatment for opening a stenotic region in a blood vessel. More particularly, the present invention relates to combination radiation and radiosensitizer delivery devices for inhibiting hyperplasia following balloon angioplasty and other interventional treatments.
A number of percutaneous intravascular procedures have been developed for treating stenotic atherosclerotic regions of a patient's vasculature to restore adequate blood flow. The most successful of these treatments is percutaneous transluminal angioplasty (PTA). In PTA, a catheter, having an expansible distal end usually in the form of an inflatable balloon, is positioned in the blood vessel at the stenotic site. The expansible end is expanded to dilate the vessel to restore adequate blood flow beyond the diseased region. Other procedures for opening stenotic regions include directional atherectomy, rotational atherectomy, laser angioplasty, stenting, and the like. While these procedures have gained wide acceptance (either alone or in combination, particularly PTA in combination with stenting), they continue to suffer from significant disadvantages. A particularly common disadvantage with PTA and other known procedures for opening stenotic regions is the frequent occurrence of restenosis.
Restenosis refers to the re-narrowing of an artery after an initially successful angioplasty. Restenosis afflicts approximately up to 50% of all angioplasty patients and is the result of injury to the blood vessel wall during the lumen opening angioplasty procedure. In some patients, the injury initiates a repair response that is characterized by smooth muscle cell proliferation referred to as “hyperplasia” in the region traumatized by the angioplasty. This proliferation of smooth muscle cells re-narrows the lumen that was opened by the angioplasty within a few weeks to a few months, thereby necessitating a repeat PTA or other procedure to alleviate the restenosis so that blood perfusion may be restored.
A number of strategies have been proposed to treat hyperplasia and reduce restenosis. Previously proposed strategies include prolonged balloon inflation during angioplasty, treatment of the blood vessel with a heated balloon, stenting of the region, use of radiotherapy to treat in-stent restenosis, the administration of therapeutic drugs following angioplasty, and other procedures. While these proposals have enjoyed varying levels of success, no one of these procedures is proven to be entirely successful in completely avoiding all occurrences of restenosis and hyperplasia.
As an alternative to the above mentioned therapies, the combination of radioisotope radiation and drug therapy following PTA for the inhibition of hyperplasia has also been proposed. Drug therapy infuses or releases a drug through a catheter or from a stent, while intravascular radiotherapy may configure catheters, guidewires, and stents to position a solid radioisotopic source (such as a wire, strip, pellet, seed, bead, or the like). While combination delivery of therapeutic agents with radioisotopic sources holds promise, optimum combinations of drugs and radiation have yet to be identified.
For these reasons, it would be desirable to provide improved devices and methods for inhibiting restenosis and hyperplasia following angioplasty and other interventional treatments. In particular, it would be desirable to provide improved devices, methods, and kits for delivery of new and optimum drugs in combination with ionizing radiation to a blood vessel to reduce and/or inhibit restenosis and hyperplasia rates with increased efficacy. It would further be desirable to provide such devices and methods which significantly reduce dose concentrations of the drugs and/or radiation within the vessel wall while delivering sufficiently uniform radiation dosages and promoting endothelialization of the vessel wall. At least some of these objectives will be met by the devices and methods of the present invention described hereinafter.
2. Description of Background Art
Full descriptions of exemplary x-ray sources for use in the present invention are described in co-pending U.S. patent application Ser. No. 09/299,304, assigned to the assignee herein, and U.S. Pat. No. 6,095,966, licensed to the assignee herein. Devices and methods for exposing intravascular and other treatment locations to radioisotopic materials in combination with therapeutic drugs are described in the following: U.S. Pat. Nos. 6,149,574; 5,993,374; 5,951,458; and International Publication Nos. WO 00/47197; WO 00/00238; WO 99/55285; WO 99/51299; WO 98/36790; and WO 96/23543. The use of texaphyrins for radiation sensitization is described in U.S. Pat. No. 6,072,038. Devices and methods for exposing intravascular locations to radioactive materials are described in the following: U.S. Pat. Nos. 6,069,938; 5,971,909; 5,653,736; 5,643,171; 5,624,372; 5,618,266; 5,616,114; 5,540,659; 5,505,613; 5,503,613; 5,498,227; 5,484,384; 5,411,466; 5,354,257; 5,302,168; 5,256,141; 5,213,561; 5,199,939; 5,061,267; and 5,059,166, European applications 860 180; 688 580; 633 041; and 593 136, and International Publications WO 97/07740; WO 96/14898; and WO 96/13303. Drug delivery within the vasculature is described in U.S. Pat. Nos. 6,099,561; 6,071,305; 6,063,101; 5,997,468; 5,980,551; 5,980,566; 5,972,027; 5,968,092; 5,951,586; 5,893,840; 5,891,108; 5,851,231; 5,843,172; 5,837,008; 5,769,883; 5,735,811; 5,700,286; 5,681,558; 5,679,400; 5,649,977; 5,637,113; 5,609,629; 5,591,227; 5,551,954; 5,545,208; 5,500,013; 5,464,450; 5,419,760; 5,411,550; 5,342,348; 5,286,254; and 5,163,952. Biodegradable materials are described in U.S. Pat. Nos. 5,876,452; 5,656,297; 5,543,158; 5,484,584; 4,897,268; 4,883,666; 4,832,686; and 3,976,071.
The disclosure of this application is related to the disclosures of the following co-pending applications being filed on the same day: U.S. patent application Ser. Nos. 09/850,721 and 09/850,728.
The full disclosures of each of the above references are incorporated herein by reference.